Vascular Smooth Muscle Cell Durotaxis Depends on Substrate Stiffness Gradient Strength
Vascular Smooth Muscle Cell Durotaxis Depends on Substrate Stiffness Gradient Strength
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DOI：
10.1016/j.bpj.2009.06.021
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发表时间：
2009-09-02
影响因子：
3.4
通讯作者：
Wong, Joyce Y.
中科院分区：
文献类型：
--
作者：
Isenberg, Brett C.;DiMilla, Paul A.;Wong, Joyce Y.
机械顺应性正在成为一种重要的环境线索，可以影响某些细胞行为，例如形态和运动性。最近的体外研究表明，细胞优先迁移从较低的刚性更硬的基板，然而，这种现象，称为硬旋转，仍然不明确。为了解决这个问题，我们研究了血管平滑肌细胞在定义明确的刚度梯度的形态和运动。基线的细胞扩展，极化，和随机运动的均匀凝胶与模量范围从5至80千帕被发现增加刚度。随后对血管平滑肌细胞在梯度基质（0-4 kPa/100 μ m，绝对模量为1-80 kPa）上的行为进行分析，结果表明梯度凝胶上的形态与绝对模量相关。与此相反，durotaxis（定量评价为有偏见的持续随机游走的战术指数）和细胞方向的梯度都随着梯度的大小增加，但独立的绝对模量。这些观察结果提供了一个基础，为建立定量关系梯度基板刚度和细胞反应。此外，这些结果揭示了细胞对趋化性和durotactic梯度的现象学反应的共同特征，激发了细胞如何整合和响应多个复杂信号的进一步机制研究。
Mechanical compliance is emerging as an important environmental cue that can influence certain cell behaviors, such as morphology and motility. Recent in vitro studies have shown that cells preferentially migrate from less stiff to more stiff substrates; however, much of this phenomenon, termed durotaxis, remains ill-defined. To address this problem, we studied the morphology and motility of vascular smooth muscle cells on well-defined stiffness gradients. Baselines for cell spreading, polarization, and random motility on uniform gels with moduli ranging from 5 to 80 kPa were found to increase with increasing stiffness. Subsequent analysis of the behavior of vascular smooth muscle cells on gradient substrata (0-4 kPa/100 mu m, with absolute moduli of 1-80 kPa) demonstrated that the morphology on gradient gels correlated with the absolute modulus. In contrast, durotaxis (evaluated quantitatively as the tactic index for a biased persistent random walk) and cell orientation with respect to the gradient both increased with increasing magnitude of gradient, but were independent of the absolute modulus. These observations provide a foundation for establishing quantitative relationships between gradients in substrate stiffness and cell response. Moreover, these results reveal common features of phenomenological cell response to chemotactic and durotactic gradients, motivating further mechanistic studies of how cells integrate and respond to multiple complex signals.